What interventions have been shown to provide clinical benefit in those assessed to be at high risk of new primary melanoma?

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Introduction

See Diagnostic aids for melanoma for detailed evidence and recommendations on early melanoma diagnosis, which has been shown to be effective in detecting subsequent melanomas at an early stage, and is therefore inferred to reduce mortality.

There is variation among international guidelines about how best to identify and manage high-risk patients.[1] The 2010 Australian guidelines recommended surveillance intervals should be based on assessment of the level of future risk of melanoma, and on the basis of expert opinion have recommended that individuals at high risk of melanoma and their partner or carer be “educated to recognise and document lesions suspicious of melanoma, and to be regularly checked by a clinician with six-monthly full body examination supported by total body photography and dermoscopy as required”.[2] Randomised comparisons of alternative screening methodologies and intervals have not been done, and are unlikely ever to be.

Systematic review evidence

The systematic review searched for studies in which a surveillance protocol reported key outcomes of incidence and thickness of prospectively detected melanoma, from which benefits to mortality and morbidity could be inferred. Two studies have reported the incidence and characteristics of melanomas detected prospectively in cohorts selected for high future risk of melanoma, using a systematic protocol of examination.[3][4] In Spain[3] and Australia[5] digital dermoscopy with reference to total body photography was used at average six-monthly intervals to monitor cohorts of individuals at high risk, defined by multiple criteria: increased numbers of atypical naevi, or a strong family history, or presence of a strong melanoma-predisposing mutation. Both studies were therefore of individuals at very high risk of melanoma, comprising less than 1% of the population. In a further French study conducted in primary care[4], the only entry criterion was increased risk based on age, and no systematic protocol of examination was followed.

Over a median eight years follow-up the Spanish study[3] identified 98 melanomas in 78 patients in a cohort of 618, at a ratio of excised benign:malignant melanocytic lesions of 10.7:1 and median Breslow thickness of 0.5mm. The Australian study[5] reported results after median 3.5 years follow-up, identifying 61 melanomas in 48 patients of a cohort of 311, at a ratio of excised benign:malignant (including in situ) melanocytic lesions of 4.4:1 and the median Breslow thickness was in situ. Both studies therefore report prima facie evidence of clinical benefit to those screened, but the results of Moloney 2014, also suggested there was potential for significant cost-benefit, due to the very low ratio of benign:malignant lesions excised.[5]

In the Moloney et al (2014) cohort,[5] microcosting analyses were therefore performed and were compared with costs of usual care using the 45 and Up study cohort (2008).[6] These comparisons confirmed a significant cost-benefit for the structured surveillance protocol.[7] Specialised surveillance was both less expensive and more effective than standard care. The mean saving was A$6,828 per patient, and the mean quality-adjusted life-year gain was 0.31.[7] The main drivers of the differences were detection of melanoma at an earlier stage resulting in less extensive treatment and a 70% lower annual mean excision rate for suspicious lesions in specialized surveillance compared with standard care.The results were robust when tested in sensitivity analyses.[7] These data have not yet been replicated elsewhere but expansion cohorts are under study. A critical factor for exploration in future research is the extent to which reduced rates of excision can be sustained in all clinical practice contexts in which such individuals are under surveillance. Finally, these outcomes confirm that a structured approach to both clinical assessment of future risk of melanoma, and to surveillance, stand to deliver real benefits to patients and the health care system more broadly. It is not yet known whether these cost-effectiveness advantages apply to patients at less extreme levels of risk.

In summary, a structured surveillance protocol, using six-monthly full skin examination, supported by dermoscopy with reference to total body photography provided clinical benefit to individuals at very high risk of melanoma, and according to Australian data does so at significant cost-benefit.

Evidence summary and recommendations

Evidence summary Level References
A structured surveillance protocol of full skin examination using dermoscopy, supported by total body photography, provides clinical benefit to individuals at very high risk of melanoma by detecting incident melanomas at an earlier stage, and according to Australian data is cost-effective. III-3 [3], [5], [7]
Evidence-based recommendationQuestion mark transparent.png Grade
Individuals at very high risk of melanoma and their partner or carer should be educated to recognise and document lesions suspicious of melanoma. These individuals should be checked regularly by a clinician with six-monthly full skin examination supported by total body photography and dermoscopy.
C


Issues requiring more clinical research study

In principle, randomised controlled trials of alternative surveillance protocols are needed, but are unlikely, for ethical reasons, ever to be done. The surveillance protocols trialled so far in very high-risk individuals should be tested in individuals at high, but lower, levels of risk.

References

  1. Watts CG, Dieng M, Morton RL, Mann GJ, Menzies SW, Cust AE. Clinical practice guidelines for identification, screening and follow-up of individuals at high risk of primary cutaneous melanoma: a systematic review. Br J Dermatol 2015 Jan;172(1):33-47 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25204572.
  2. Australian Cancer Network Melanoma Guidelines Revision Working Party. Clinical Practice Guidelines for the Management of Melanoma in Australia and New Zealand. Wellington: Cancer Council Australia and Australian Cancer Network, Sydney and New Zealand Guidelines Group; 2008.
  3. 3.0 3.1 3.2 3.3 Salerni G, Carrera C, Lovatto L, Puig-Butille JA, Badenas C, Plana E, et al. Benefits of total body photography and digital dermatoscopy ("two-step method of digital follow-up") in the early diagnosis of melanoma in patients at high risk for melanoma. J Am Acad Dermatol 2012 Jul;67(1):e17-27 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21683472.
  4. 4.0 4.1 Rat C, Grimault C, Quereux G, Dagorne M, Gaultier A, Khammari A, et al. Proposal for an annual skin examination by a general practitioner for patients at high risk for melanoma: a French cohort study. BMJ Open 2015 Jul 29;5(7):e007471 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26224016.
  5. 5.0 5.1 5.2 5.3 5.4 Moloney FJ, Guitera P, Coates E, Haass NK, Ho K, Khoury R, et al. Detection of primary melanoma in individuals at extreme high risk: a prospective 5-year follow-up study. JAMA Dermatol 2014 Aug;150(8):819-27 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24964862.
  6. Banks E, Redman S, Jorm L, Armstrong B, Bauman A, Beard J, et al. Cohort profile: the 45 and up study. Int J Epidemiol 2008 Oct;37(5):941-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17881411.
  7. 7.0 7.1 7.2 7.3 Watts CG, Cust AE, Menzies SW, Mann GJ, Morton RL. Cost-Effectiveness of Skin Surveillance Through a Specialized Clinic for Patients at High Risk of Melanoma. J Clin Oncol 2017 Jan;35(1):63-71 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28034073.

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